Procyanidin B2 improves endothelial progenitor cell function and promotes wound healing in diabetic mice <i>via</i> activating Nrf2

Fan, Jianwei; Liu, Hairong; Wang, Jinwu; Zeng, Jie; Tan, Yi; Wang, Yashu; Yu, Xiaoping; Li, Wenlian; Wang, Peijian; Zheng, Yang; Dai, Xiaozhen

doi:10.1111/jcmm.16111

Cited by 48 publications

(28 citation statements)

References 49 publications

(123 reference statements)

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“…hyperglycemia. Hyperglycemia has been shown to delay diabetic wound healing by inducing dysfunction in the vascular endothelial cells (Fan et al, 2021). Therefore, the improvement of glucolipid metabolism disorders is one of the most effective strategies for the treatment of diabetes and related complications.…”

Section: Discussionmentioning

confidence: 99%

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

Zhao

Lin

et al. 2021

Front. Pharmacol.

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Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mouse model of T2D stroke. Angiogenesis plays an important role in neuronal survival and functional recovery post-stroke. NmFGF1 promoted angiogenesis in the mouse model of T2D stroke. Furthermore, nmFGF1 reversed the reduction of tube formation and migration in human brain microvascular endothelial cells (HBMECs) cultured in high glucose conditions and treated with oxygen glucose deprivation/re-oxygenation (OGD). Amp-activated protein kinase (AMPK) plays a critical role in the regulation of angiogenesis. Interestingly, we found that nmFGF1 increased the protein expression of phosphorylated AMPK (p-AMPK) both in vivo and in vitro. We found that nmFGF1 promoted tube formation and migration and that this effect was further enhanced by an AMPK agonist (A-769662). In contrast, these processes were inhibited by the application of an AMPK inhibitor (compound C) or siRNA targeting AMPK. Furthermore, nmFGF1 ameliorated neuronal loss in diabetic stroke mice via AMPK-mediated angiogenesis. In addition, nmFGF1 ameliorated glucose and lipid metabolic disorders in our mouse model of T2D stroke without causing significant changes in body weight. These results revealed that nmFGF1-regulated glucolipid metabolism and angiogenesis play a key role in the improvement of functional recovery in a mouse model of T2D stroke and that these effects are mediated by the AMPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

Zhao

Lin

et al. 2021

Front. Pharmacol.

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“…To evaluate effects of EMPA on oxidative stress in heart tissues and PA-treated H9C2 cells, dihydroethidium (DHE) (Molecular Probes, Eugene, OR, USA) superoxide anion fluorescent probe staining was performed to evaluate the oxidative stress level of frozen heart sections and H9C2 cells, as described in our previous research [ 26 ]. Briefly, frozen heart sections of the left ventricle were incubated with 5 μ M DHE in a dark and humidified container at 37°C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Empagliflozin Ameliorates Diabetic Cardiomyopathy via Attenuating Oxidative Stress and Improving Mitochondrial Function

Liu

Tian

Dai

2022

Oxidative Medicine and Cellular Longevity

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Diabetic cardiomyopathy (DCM) is considered to be a critical contributor to the development of heart failure. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has been shown to prevent cardiovascular events and reduce the incidence of heart failure in randomized clinical trials. However, the mechanism of how EMPA prevents DCM is poorly understood. To study the potential mechanisms involved in the therapeutic effects of EMPA, we assessed the protective effects of EMPA on myocardial injury in type 2 diabetic db/db mice and H9C2 cardiomyocytes. 9–10-week-old male db/db mice were treated with EMPA (10 mg/kg) via oral gavage daily for 20 weeks. Afterward, cardiac function of treated mice was evaluated by echocardiography, and pathological changes in heart tissues were determined by histopathological examination and western blot assay. EMPA markedly reduced blood glucose levels, improved insulin tolerance, and enhanced insulin sensitivity of db/db mice. In addition, EMPA significantly prevented cardiac dysfunction, inhibited cardiac hypertrophy and fibrosis, and reduced glycogen deposition in heart tissues. Furthermore, EMPA improved diabetes-induced oxidative stress and mitochondrial dysfunction in both heart tissues of db/db mice and palmitate exposed H9C2 cells. EMPA significantly increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genetic targets in cardiac tissue of type 2 diabetic db/db mice and H9C2 cells. EMPA also downregulated the expression of mitochondrial fission-related proteins and upregulated the expression of mitochondrial fusion-related proteins. Collectively, these findings indicate that EMPA may prevent DCM via attenuating oxidative stress and improving mitochondrial function in heart tissue.

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“…Nrf2 activation in fibroblasts is also induced by many natural compounds including polyphenols, such as curcumin, epigallocatechin-3-gallate (EGCG) or apomorphine, and flavone derivatives as well as many bioactive components of pepper beetle, brassica plants and walnut sprouts extracts [ 120 ]. Similarly, procyanidin B2, one of the major bioactive components of procyanidins promotes wound healing in diabetic mice in a Nrf2-dependent manner [ 86 ]. Curcumin, a potent Nrf2 activator, accelerated the cutaneous wound healing in streptozotocin-induced diabetic rat model [ 121 ].…”

Section: Nrf2 Induction Of Cytoprotective Genes and Nrf2 Dependent Therapeutic Regimens In Wound Healingmentioning

confidence: 99%

“…Schmidt et al showed that cold plasma promotes Nrf2-and p53-mediated granulation and reepithelization in the skin of SKH1 mice. Levels of proinflammatory cytokines IL-6 or TNFα and angiogenetic factors such as FGF, KGF, VEGF and COX2 increase in the early stages [86] in vitro in vivo Cutaneous wound i.p. injection (10 mm dorsal skin) siKeap1…”

Section: The Role Of Nrf2 In Cell Proliferation Apoptosis and Migration During Wound Repairmentioning

confidence: 99%

Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process

Süntar

Çetinkaya²,

Panieri

et al. 2021

Molecules

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Wound healing involves a series of cellular events in damaged cells and tissues initiated with hemostasis and finally culminating with the formation of a fibrin clot. However, delay in the normal wound healing process during pathological conditions due to reactive oxygen species, inflammation and immune suppression at the wound site represents a medical challenge. So far, many therapeutic strategies have been developed to improve cellular homeostasis and chronic wounds in order to accelerate wound repair. In this context, the role of Nuclear factor erythroid 2-related factor 2 (Nrf2) during the wound healing process has been a stimulating research topic for therapeutic perspectives. Nrf2 is the main regulator of intracellular redox homeostasis. It increases cytoprotective gene expression and the antioxidant capacity of mammalian cells. It has been reported that some bioactive compounds attenuate cellular stress and thus accelerate cell proliferation, neovascularization and repair of damaged tissues by promoting Nrf2 activation. This review highlights the importance of the Nrf2 signaling pathway in wound healing strategies and the role of bioactive compounds that support wound repair through the modulation of this crucial transcription factor.

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Procyanidin B2 improves endothelial progenitor cell function and promotes wound healing in diabetic mice via activating Nrf2

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 48 publications

References 49 publications

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

Empagliflozin Ameliorates Diabetic Cardiomyopathy via Attenuating Oxidative Stress and Improving Mitochondrial Function

Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process

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